Revealing pharmacodynamics of medicinal plants using in silico approach: a case study with wet lab validation

Exploration of therapeutic mechanism is an integral part of medicinal plant based drug discovery for better understanding of pharmacological behavior of these agents. But, its study using conventional hit and trial wet laboratory experiments proves to be very tedious, time consuming and expensive, thus encouraging development of in silico techniques. Hence, an in silico technique has been devised using a computer software Prediction of Activity Spectra for Substances (PASS) to study pharmacodynamics of medicinal plants. The technique has been presented with a case study using Ficus religiosa L. (Moraceae) in which its anticonvulsant mechanism has been elucidated with PASS and further validated experimentally.

Pentylenetetrazol (PTZ)-induced convulsion test was used to study the anticonvulsant effect of standardized bark extract of F. religiosa. Thereafter, structure of all the reported bioactive metabolites in the bark was subjected to PASS software to obtain biological activity spectrum of each compound. The mechanism signifying anticonvulsant effect was selected from the spectrum and was further validated using in vitro test.

The extract showed significant anticonvulsant effect in PTZ test. PASS analysis showed a high activity score for GABA aminotransferase (GABA-AT) inhibitory effect of the bioactive metabolites present in the bark. In vitro GABA-AT enzyme assay results were in concordance with the predicted mechanism by PASS for the observed anticonvulsant effect, as the extract showed potent inhibition of the enzyme. The results of present study showed the in silico technique to be useful for elucidation of unknown therapeutic mechanisms of medicinal plants.